Dyslipidemia (Lecture 5)

Question 1

The most common clinical manifestation of lipid disorders is atherosclerotic cardiovascular disease (ASCVD) resulting from elevated levels of

Answer 1

apo B-100 lipoproteins

Question 2

Severe hypertriglyceridemia is primarily associated with an increased risk of

Answer 2

pancreatitis.

Question 3

The rate-limiting step in cholesterol synthesis is the reduction to mevalonate by 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase, the target of

Answer 3

statins.

Question 4

LDL is removed from the blood predominantly by the LDL receptor. LDL receptor expression is regulated by ______. Inhibition or decreased levels of _____ thus permit greater LDL receptor circulation and enhanced LDL particle removal from the circulation.

Answer 4

proprotein convertase subtilisin/kexin type 9 (PCSK9)

Question 5

Apo B lipoproteins, as measured by total, ____ and non-HDL-C levels, predict ASCVD risk in all ages, genders, races/ethnicities, and regions.

Answer 5

LDL-C

Question 6

All patients with a first LDL-C of ___ mg/dL or higher or triglycerides of 500 mg/dL or higher should be evaluated for secondary causes of hyperlipidemia

Answer 6

160

Question 7

The LDL-C lowering agents ____ and PCSK9 monoclonal antibodies have been shown to further reduce car- diovascular events when added to background statin therapy in very-high- risk patient populations.

Answer 7

ezetimibe

Question 8

4 statin benefit groups…
1. Clinical ASCVD

2. LDL-C higher than 190 mg/dL
3. _____
4. ____

Answer 8

3. Individuals 40-75 years of age with diabetes with LDL-C 70-189 mg/dL
4. Individuals 40 to 75 years of age with LDL-C 70-189
   mg/dL AND an estimated 10-year ASCVD risk of >7.5%

Question 9

In patients with heart failure with reduced ejection fraction attributable to ischemic heart disease who have a reasonable life expectancy and are not already on a statin because of ASCVD, clinicians may consider initiation of ____-intensity statin therapy to reduce the occurrence of ASCVD events.

Answer 9

moderate

Question 10

High intensity statins?

Answer 10

Atorvastatin 40-80

Rosuvastatin 20

Question 11

Low-intensity statins?

Answer 11

Pravastatin 10-20

Lovastatin 20

Question 12

The most straightforward approach in patients with mild to moderate symptoms is to stop the statin, wait until symptoms resolve, and rechallenge with the same statin at a lower dose or another statin at least once a week, depending on the patient’s preferences after being informed of statin benefits (heart attack, stroke, and death reduction). If symptoms do not resolve within ___, the statin is not the cause

Answer 12

2 months

Question 13

Symptomatic creatine kinase elevations more than 10 times the upper limit of normal, elevated creatinine levels, and myoglobinuria are indicative of ____. The statin should be stopped and the patient should be admitted to the hospital for hydration, close observation, and evaluation for other causes of severe muscle damage.

Answer 13

rhabdomyolysis

Question 14

Statins have no hepatotoxic effects. If transaminases are ___ times the upper limit of normal, then alanine aminotransferase can be retested in 3 months as reassurance of continued statin safety.

Answer 14

2-3

Question 15

Two PCSK9 monoclonal antibodies, alirocumab and evolocumab, and ____ have been shown to futher reduce ASCVD risk when added to background statin therapy in high risk ASCVD patients.

Answer 15

ezetimibe

Question 16

____ is contraindicated for use with statin therapy due to a greater than 30-fold increased risk of myopathy.

Answer 16

Gemfibrozil

Question 17

Ezetimibe acts in the small intestine to block cholesterol uptake by the Niemann- Pick C1-Like 1 receptor. The resulting lower level of intrahepatic cholesterol stimulates synthesis of ___

Answer 17

LDL-C receptors

Question 18

Early plaque growth typically involves a compensatory outward remodeling of the arterial wall that preserves the diameter of the lumen and permits plaque accumulation without limitation of blood flow, hence producing no ischemic symptoms. Lesions at this stage can thus evade detection by ___

Answer 18

angiography

Question 19

Atherosclerotic plaques do not distribute homogeneously throughout the vasculature. They usually develop first in the dorsal aspect of the ____ and proximal coronary arteries, followed by the popliteal arteries, descending thoracic aorta, internal carotid arteries, and renal arteries.

Answer 19

abdominal aorta

Question 20

Ejection clicks are high-pitched sounds that occur at the moment of maximal opening of the aortic or pulmonary valves. … Ejection clicks may also be called ejection sounds. The ____ correlate of the ejection click is the opening snap, which occurs at maximal opening of a flexibly stenotic mitral or tricuspid valve.

Answer 20

diastolic

Question 21

The metabolic syndrome (also known as the “insulin resistance syndrome”) refers to a cluster of risk factors, including hypertension, hypertriglyceridemia, ____,___, and visceral obesity

Answer 21

reduced HDL, hyperglycemia

Question 22

__ has shown the greatest promise as a marker of low-grade systemic inflammation associated with atherosclerotic disease.

Answer 22

CRP

Although it serves as a marker of risk not captured by traditional algorithms, CRP itself does not mediate atherogenesis.

Question 23

Beta lipoprotein aka?

Answer 23

LDL

Question 24

The most common clinical manifestation of lipid disorders is atherosclerotic cardiovascular disease (ASCVD) resulting from elevated level of

Answer 24

apo B-100 lipoproteins.

Triglcycerides are not known to be a risk factor for CVD!

Question 25

____ inhibit the rate-limiting step in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA reductase) which bind acetyl CoA to free cholesterol to create cholesterol esters.

Answer 25

Statins

Question 26

When do we start monitoring LDL? What about BP?

Answer 26

LDL monitoring starting between 9-11 y/o (maybe earlier if at risk)

BP between 5-6 y/o

Question 27

You can use an ___ to get a Calcium score

Answer 27

EBCT

Question 28

You shouldn’t mix fibrates and statins…

Answer 28

check

Question 29

USPTF/AHAH recommend screening at least once every 5 years for all people over age ___

ACC/AHA recommend calculating the ASCVD risk every ___ for those 40-75 y/o w/o ASCVD or DM w/ LDL at 70-189 mg/dL

Answer 29

20

4-6 years

Question 30

Many things predispose individuals to statin adverse effects, like?

Answer 30

Unexplained ALT elevations > 3x normal

all the others makes sense

Question 31

Remember to establish a baseline of muscle symptoms before starting on statins

Answer 31

You hope to avoid the unnecessary discontinuation of statins

However, w/ SEVERE muscle sxs, d/c the statins and work up for possible rhabdo (CK, creatinine, UA for myoglobinuria)

Question 32

Mild, moderate muscle pains on statin?

Answer 32

D/c statin and Assess for other conditions..

When sxs resolve, start SAME statin (maybe a lower dose) and then monitor for the symptom-drug relationship

If sxs arise again, d/c original statin, let sxs resolve and start a low-dose if different statin

Question 33

After ___ months of no statin treatment, muscle symptoms or CK
levels do not resolve search for secondary cause

• Should symptoms be found to be unrelated to statin therapy, or if
predisposing condition treated, RESUME statin therapy at the
original dose

Answer 33

2

Question 34

1. Individuals with clinical ASCVD
2. Individuals with primary elevations of LDL-C ≥ 190
   mg/dL
3. Individuals 40-75 years of age with diabetes with LDL-
   C 70-189 mg/dL
4. Individuals 40 to 75 years of age with LDL-C 70-189
   mg/dL AND an estimated 10-year ASCVD risk of >7.5%

Answer 34

4 statin benefit groups

Question 35

ASCVD includes?

Answer 35

CHD, stroke, and peripheral artery dz (think this when have diminished pulses)

Question 36

Remember those > 75 y/o only get moderate intensity statin

Answer 36

k

Question 37

Unexplained ALT> 3x?

Answer 37

No statin

Question 38

High intensity statin therapy reduces LDL by how much?

Answer 38

50%

remember, even if patient has positive response, reinforce adherence at 3,12 mos

Question 39

LDL>190?

Answer 39

HIGH INTENSITY STATIN

Atorvastatin 40-80
Rosuvastatin 20

Question 40

Benefit group 1… Individuals with ASCVD… when wouldn’t you give HIGH INTENSITY STATIN?

(these individuals normally get HIGH INTENSITY STATINs, so when wouldn’t they?)

Answer 40

Older than 75…

other CI, like ALT>3x

Question 41

Patients w/ DM, aged 40-75, can either get a moderate or high intensity statin? How do we decide?

Answer 41

If their 10-year ASCVD risk > 7.5 they get high intensity statin

Atorvastatin 40-80
Rosuvastatin 20

Otherwise, go moderate intensity

Question 42

Group number 4… those with a risk > 7.5, aged 40-75… they can get either mod or high…

Answer 42

Discuss with patient

Question 43

When triglcyerides are > 500, we can consider fenofibrate and gemfibrozil… However this doesn’t take precedence over statin therapy…

Answer 43

Remember you can’t combine these with statins

Remember even TAG of 499 doesn;’t get treated

Question 44

Bile acid-binding agents, such as cholestyramine, colestipol, and colesevelam, have adverse effects, most notably?

Answer 44

constipation and bloating

Question 45

Niacin can cause flushing but we can ___ to mitigate thst

Answer 45

aspirin

Question 46

Metabolic syndrome is a cluster of at least 3 of the 5…

Answer 46

Obesity
Triglycerides
HDL (less than 40 for men, less than 50 for women)
BP
Fasting glucose

Question 47

More limited data are available from cardiovascular outcomes trials
in highly selected populations for other lipid-modifying agents. The
LDL-C lowering agents ___ and ___ have been shown to further reduce
cardiovascular events when added to background statin therapy in
very-high-risk patient populations.

Answer 47

ezetimibe A7 and PCSK9 mabs

The relative reduction in ASCVD risk from all of these drugs is
proportional to the magnitude of the LDL-C or non-HDL-C lowering.

Question 48

There are two PCSK9 inhibitors available in the U.S.: ___ and ____

FDA has approved alirocumab for adult patients:

To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.
As an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce LDL-cholesterol FDA has approved evolocumab for adult patients:

To reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease.
As an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce LDL-cholesterol
As an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia who require additional lowering of LDL-C.[1]

Answer 48

alirocumab and evolocumab.

Question 49

No trials have evaluated bile acid sequestrants added to background
statin therapy. _____ is contraindicated for use with statin
therapy due to a greater than 30-fold increased risk of myopathy.

Answer 49

Gemfibrozil